title: Effects of extracellular ATP on surfactant secretion.
abstract: Extracellular ATP is the most potent endogenous stimulus for surfactant phospholipid secretion from alveolar type II cells identified to date. This effect of ATP appears mediated via a P2-purinoceptor because the rank order of agonist potency is ATP greater than ADP greater than AMP = adenosine. Examination of other ATP analogues demonstrates a rank order of agonist potency of ATP = gamma S-ATP greater than AMPPNP greater than AMPPCP greater than AMPCPP for surfactant secretion, consistent with a P2y-purinoceptor mediating this effect. This hypothesis is further supported by experiments with reactive blue 2, which selectively inhibits ATP-stimulated surfactant phospholipid secretion and has been purported as a specific inhibitor at P2y-purinoceptors. Several second messenger systems are activated in the type II cell following agonist binding: intracellular Ca2+ is mobilized, prostaglandin levels increase, and protein kinase C is activated. Of these three second messengers, protein kinase C appears to be the most important for surfactant secretion because inhibition of protein kinase C activation blocks ATP-induced surfactant secretion whereas inhibition of Ca2+ mobilization and prostaglandin production does not affect ATP-induced surfactant secretion.
authors.affiliation: Department of Pediatrics, College of Medicine, University of Cincinnati, Ohio 45267.
authors.forename: W R
authors.initials: WR
authors.lastname: Rice
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D029742:Caenorhabditis elegans Proteins; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins; D002478:Cells, Cultured; D002794:Choline / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism*; D011493:Protein Kinase C; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D011955:Receptors, Drug; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D015240:Phorbol 12,13-Dibutyrate; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D002794:Choline; D002118:Calcium